Shape-Shifting Viral Proteins: Key to HIV and COVID-19 Vaccines

By Marcella Flores, M.P.H., Ph.D.

Published Tuesday, April 7, 2020

Dr. Maolin LuScientists around the world are racing to find a vaccine for the virus causing the COVID-19 pandemic. With more than 30 years of vaccine experience, the HIV field has the expertise to take on the challenge. But one similarity between the two viruses could stand in the way of success—the shape-shifting dynamics of the surface viral proteins. Like Env, the surface protein on HIV, SARS-CoV-2 (the new coronavirus) has a spike protein that is required by the virus to enter a cell. Once the spike protein connects to the cell, it begins to change shape to force entry into the cell.

Last year, Dr. Maolin Lu was the first scientist to determine exactly which HIV Env shape was most susceptible to antibody attack and therefore a vaccine target to prevent infection. I spoke with Dr. Lu, a postdoctoral researcher at Yale University, to find out how she is applying the techniques she developed for HIV to understand the novel coronavirus’ spike protein in order to develop an effective vaccine.

Dr. Marcella Flores for amfAR: In 2019, you published a paper in the very prestigious journal Nature and it made a big splash in the HIV vaccine world. Can you tell us why?

Dr. Maolin Lu: Right now, much hope for an HIV vaccine is associated with broadly neutralizing antibodies. In that paper we raised concerns about the current vaccine candidates in clinical trials. It was very unexpected and to our great surprise we showed that the current vaccine candidate [using SOSIP to mimic Env] is targeting a [different shape], not the most critical one. This explains why those vaccines failed to induce potent broadly neutralizing antibodies [to HIV].

amfAR: Your paper showed that the vaccine field was aiming at the wrong target?

Dr. Lu: We are trying to be more positive: There is room for improvement.

amfAR: Many of the world’s labs are halting “non-essential” work right now and turning to COVID-19. So what are you working on now?

"My expertise in HIV-1 will be useful on this battlefield with the coronavirus." - Dr. Maolin LuDr. Lu: There are a lot of correlations and similarities between HIV and SARS-CoV-2. They are both enveloped viruses and have spike proteins on their surface. The spike proteins on the coronavirus surface are highly dynamic—constantly changing shape to escape being detected [by the immune system]. We will capture the different shapes and characterize them. We will use our experience from HIV and define the preference for certain shapes to use as a template for our immune system to make antibodies.

amfAR: You were last year’s recipient of our prestigious Krim Fellowship and now you find yourself in the middle of this pandemic, knee-deep in vaccine work on two arms: HIV and coronavirus. How do you think this will impact you as an early-stage investigator?

Dr. Lu: I have altered my focus for now—temporarily shifted my attention to coronavirus. But it will have a long-term impact on my future research interests. Within the past 20 years, coronaviruses have checked in to the world several times [MERS and SARS have caused outbreaks in recent years], so the basic science—the fundamental science—will provide guidelines for developing vaccines and antiviral drugs for future pandemics.

amfAR: Thank you Dr. Lu for your insights. We are very grateful and proud to call you a Krim Fellow.